intravenous bi 836826 in combination with ibrutinib in relapsed/refractory cll patients who have been pre-treated with at least one prior line of systemic therapy, and who are eligible for treatment with ibrutinib

Conditions: Leukemia, Lymphocytic, Chronic, B-Cell

Summary: intravenous bi 836826 in combination with ibrutinib in relapsed/refractory chronic lymphocytic leukemia (cll) patients who have been pre-treated with at least one prior line of systemic therapy, and who are eligible for treatment with ibrutinib. objectives of the trial are to determine the recommended phase 2 dose of bi 836826, and to document the safety and tolerability of bi 836826 when given in combination with ibrutinib


Eligibility criteria:
inclusion criteria: * diagnosis of chronic lymphocytic leukemia (cll) established according to international workshop chronic lymphocytic leukemia (iwcll) criteria. * relapsed or refractory cll pre-treated with at least one prior line of systemic therapy for cll. * indication for treatment consistent with iwcll criteria, i.e. at least one of the following criteria should be met * evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. * massive or progressive or symptomatic splenomegaly. * massive nodes or progressive or symptomatic lymphadenopathy. * progressive lymphocytosis in the absence of infection, with an increase in blood absolute lymphocyte count (alc) \>=50% over a 2-month period, or a lymphocyte doubling time (ldt) of \ =30000/µl). * autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy. * constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: * unintentional weight loss of 10% or more within the previous 6 months * significant fatigue * fevers higher than 100.5°f or 38.0°c for \>=2 weeks without other evidence of infection * night sweats for \> 1 month without evidence of infection * clinically quantifiable disease burden defined as at least one of the following: * either alc \>10 000/µl, or * measurable lymphadenopathy * quantifiable bone marrow infiltration documented in a bone marrow biopsy during screening * resolution of all clinically relevant acute non-hematologic toxic effects of any prior antitumor therapy resolved to grade \<=1 * baseline laboratory data as defined as: hemoglobin (hb): \>=8g/dl absolute neutrophil count (anc): \>=1000/µl platelet (plt): \>=25000/µl glomerular filtration rate (gfr) or creatinine clearance: \>=30ml/min aspartate aminotransferase (ast) and alanine aminotransferase (alt): \<3 x upper limit of normal (uln) bilirubin - total: \<1.5 x uln activated partial thromboplastin time (aptt), prothrombin time (pt) or international normalized ratio (inr): \<=1.5 x uln pt \<=1.5 x uln, inr \<=1.5 * male or female patients. women of childbearing potential must agree to use highly effective methods of birth control during the trial and for at least 1 year after the last dose of bi 836826 and 1 month after the last dose of ibrutinib. * eastern cooperative oncology group (ecog) performance score of 0 to 2. * age 18 years and older * eligible and able to secure sourcing for ibrutinib * written informed consent * further inclusion criteria apply exclusion criteria: * known transformation of chronic lymphocytic leukemia (cll) to an aggressive b-cell malignancy at the time of screening * prior allogeneic stem cell transplant within one year or active graft vs. host disease. * history of a non-cll malignancy except for adequately treated in situ, stage 1 or 2 carcinoma in complete response (cr), or any other cancer that has been in cr for \>=2 years after end of cancer treatment. * active, uncontrolled autoimmune cytopenia. patients with autoimmune cytopenia which is controlled with corticosteroids at doses of \<=20 mg prednisolone or equivalent may be enrolled. * previous cll treatment with a cd37-targeting antibody or a cd37-antibody drug conjugate. * previous treatment with ibrutinib * previous treatment with another bruton's tyrosine kinase (btk) -inhibitor. * ongoing systemic immunosuppressive therapy other than corticosteroids. * active bacterial, viral, or fungal infection requiring systemic treatment at the time of study entry. * human immunodeficiency virus (hiv) infection * active hepatitis b or c as evidenced by detection of virus specific deoxyribonucleic acid (dna) or ribonucleic acid (rna). * history of stroke or intracranial hemorrhage within 6 months prior to enrollment * chronic persistent atrial flutter or atrial fibrillation. patients with intermittent atrial fibrillation may be enrolled if without episode for \>= 6 months and without indication for anti-coagulation * requirement for chronic anticoagulation with warfarin or with direct oral anticoagulants at the time of screening. * chronic treatment (i.e. \>7 days) with a strong cytochrome p450 (cyp3a) inhibitor which cannot be terminated prior to the first dose of ibrutinib. * unstable angina pectoris, uncontrolled hypertension, uncontrolled asthma or other pulmonary disease * women who are pregnant, nursing, or who plan to become pregnant while in the trial * further exclusion criteria apply